1. Field of the Invention
The invention relates to a pharmaceutical lozenge for the modified release of active compounds in the gastrointestinal tract, with active-compound-containing particles which have a first coating controlling the release and a further, outer coating with saliva-resistant properties.
2. Description of the Prior Art
Orally administrable presentation forms having modified active compound release can serve various therapeutic aims. The most frequent aims are the protection of the gastric mucosa from a harmful active compound or the protection of the active compound from the acidic medium in the stomach on the one hand, which is brought about by enteric coatings; moreover the control of the release rate over a relatively long time, which can be achieved by various release-delaying measures and leads to plasma levels with relatively low variations, a better tolerability as a result and a longer efficacy of the administration.
A formulation with modified active-compound release cannot be equally easily developed in the case of all pharmacologically suitable active substances. As a rule, it necessitates a number of additives with the aid of which the desired effects can be achieved. These additives correspondingly clearly increase the mass of the presentation form. In presentation forms with prolonged release of active compound, the dose to be administered is additionally increased compared to a simple presentation form. In the case of various active compounds, on account of their dose, no presentation forms having prolonged release of active compound could be developed using the possibilities known until now, since they could not be swallowed in the form of a capsule or tablet because of the resulting dimensions. Thus various antibiotics, for example, must still be orally administered three to four times daily although it is known that in the case of administration more than twice daily the reliability of taking by patients is low. In the case of antibiotics, the non-delayed-release single dose is frequently already 500 to 1000 mg, which together with the auxiliaries necessary for pharmaceutical formulation leads to capsules or tablets which can only be swallowed with difficulty. A delayed-release preparation prepared on the basis of conventional techniques with more than 1000 mg of active compound and an increased content of auxiliaries can virtually no longer be swallowed.
The provision of a presentation form which is easy and pleasant to take with modified release of active compound, which is also suitable for active compounds which have to be taken in high single doses, is desirable.
According to the invention, the problem of the taking of high doses should first of all be solved by administering a multiparticulate active compound preparation which is compressed to give a lozenge, whose particles are individually coated to achieve a modified release. The coated particles are released in finely divided form on sucking the tablet in the mouth and can be easily swallowed with the saliva.
The presentation form of the lozenge has been known for a long time and is frequently used in order to deliver active compounds to the diseased oral and pharyngeal mucosa. The lozenge can also be suitable for systemically active substances if the substances have a pleasant taste and are to be absorbed without delay. For the solution of the problem, the presentation form of the lozenge is employed, since it is able to accommodate more active-compound and auxiliary mass without loss of its administrability than a tablet intended for swallowing. Lozenges having a mass of more than 4 g are on the market and are apparently accepted by patients without problem.
In principle, the prior art allows the compression of coated particles having modified release of active compound, although the intended use according to the invention with its advantages--administration as a lozenge with suitability even for high doses of active compound--was neither recognized nor described as a solution of the problem presented above.
Thus the Patent Applications EP 153 104 and EP 355 247 teach, for example, the compression of release-delaying coated particles containing active compound to give tablets, a process which is also described in other sources. Moreover, the Patent Specification U.S. Pat. No. 5,464,632 discloses a rapidly disintegrating tablet intended for sucking or for disintegration in the mouth, which contains the active compound optionally in the form of coated particles for modified release. However, with this tablet in the case of disintegration in the mouth it is to be expected that portions of the active compound have already been released through the coating of the particles into the oral cavity and in the course of this leaves behind an adverse taste impression.
Analogously, the presentation form of the lozenge, as is claimed in the present invention, does also solve, on the one hand, the problem of the administrability of relatively large amounts of active compound and auxiliaries, but on the other hand creates new problems. For one thing, in the case of enteric-coated particles the coatings are exposed to the pH-neutral saliva, as a result of which they prematurely disintegrate and can no longer achieve the desired protective effect in the stomach. For another thing, in the case of particles which are provided with release-delaying coatings, portions of the active compound have already been released in the oral cavity by diffusion, which is not acceptable, in particular in the case of unpleasantly tasting substances.